TY - JOUR
T1 - Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD
T2 - Results from the FLAME study
AU - Anzueto, Antonio R.
AU - Kostikas, Konstantinos
AU - Mezzi, Karen
AU - Shen, Steven
AU - Larbig, Michael
AU - Patalano, Francesco
AU - Fogel, Robert
AU - Banerji, Donald
AU - Wedzicha, Jadwiga A.
N1 - Funding Information:
The authors would like to thank patients and staff at the participating centers. The authors would also like to thank Chiranjit Ghosh, PhD and Ian Wright, PhD (professional medical writers, Novartis) for assistance in the preparation of this manuscript, as well as Jessie Wang (senior principal biostatistician, Novartis) for statistical analysis support. Writing support was funded by the study sponsor.
Funding Information:
The FLAME study was sponsored by Novartis Pharma AG. The study sponsor was involved in the design of the study and collection, and analysis of the data. The authors had full access to all of the data and this manuscript represents their interpretation of the data.
Funding Information:
AA has received honoraria for consultant services and speaking from Novartis, AstraZeneca, Boehringer Ingelheim, Sunovion Pharma, and GlaxoSmithKline. JAW has received no honoraria for lectures, consultant services and/or advisory boards. She has received research grants from Novartis, AstraZeneca, Boehringer Ingelheim, Johnson and Johnson, Sunovion Pharma, GlaxoSmithKline. KK is an employee and shareholder at Novartis Pharma AG. KK has previously received honoraria for speeches and consulting services from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN and Takeda, outside the submitted work. None of the authors received any compensation for the development of the manuscript.
PY - 2018/6/20
Y1 - 2018/6/20
N2 - Background: Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study. Methods: CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St. George's Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID-) at Week 12. Results: IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID- patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID- patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID- patients. Conclusions: IND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.
AB - Background: Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study. Methods: CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St. George's Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID-) at Week 12. Results: IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID- patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID- patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID- patients. Conclusions: IND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.
KW - CID
KW - COPD
KW - Chronic obstructive pulmonary disease
KW - Clinically important deterioration
KW - FLAME
KW - Indacaterol/glycopyrronium
KW - LABA/LAMA
KW - Salmeterol/fluticasone
UR - http://www.scopus.com/inward/record.url?scp=85048856159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048856159&partnerID=8YFLogxK
U2 - 10.1186/s12931-018-0830-z
DO - 10.1186/s12931-018-0830-z
M3 - Article
C2 - 29925383
AN - SCOPUS:85048856159
VL - 19
JO - Respiratory Research
JF - Respiratory Research
SN - 1465-9921
IS - 1
M1 - 121
ER -